Neisseria gonorrhoea is an organism for which the human host is the only known niche. As with most pathogens, the first step in the infectious process is adherence to host tissue. Early studies in human volunteers revealed that Neisserial pili are essential for the establishment of an infection. Therefore, pili, specifically type 4 pili, appear to be an essential virulence factor for Neisseria. An adherence factor, PilC1, associated with Neisserial pili has been shown to be required for specific interaction with host tissue. Both N. gonorrhoea and N. meningitidis have two versions, PilC1 and PilC2, of this adhesin. A PilC1 homologue, PilY1, was recently discovered in Pseudomonas aeruginosa. Bacteroides nodosus, Moraxella bovis, Vibrio cholerae, enterotoxigenic E. coli and enteropathogenic E. coli also produce type 4 pili. It is likely that PilC1 homologues, which function as adhesins, will be discovered in each of these pilus systems. We propose to clone, over-express, purify and develop PilC1 and PilC2 as vaccine candidates. The efficacy of this protein as a potent immunogen will be shown in an experimental rat-pup model for N. gonorrhoea infection and will serve to validate subsequent testing of this vaccine in humans. PROPOSED COMMERCIAL APPLICATIONS: Gonorrhea remains one of the most common sexually transmitted diseases causing significant morbidity and imposing a great burden on health care system. Increasing frequency of antibiotic resistance threaten to worsen the situation. Experiments outlined in this proposal will test a prototype vaccine in animals. If successful this preclinical data will serve as basis for subsequent human trials in Phase II